Impact of bariatric surgery on RNA-seq gene expression profiles of peripheral monocytes in humans
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ABSTRACT: Genome-wide expression profiles in peripheral monocytes (PM) from 19 obese women before and 3 months after bariatric surgery using the RNA-seq technology. This dataset is linked to the dataset GSE65540 providing expression profiles in subcutaneous adipose tissue (SAT) in the same population. Due to exclusion of some individuals for technical reasons, the overlap between the 2 datasets is of 18 women. mRNA sequencing of peripheral monocyte (PM) samples from 19 obese women before and 3 months after bariatric surgery
Project description:Bariatric surgery is the most effective therapy of severe human obesity. It is associated with improvements in metabolic and non metabolic co-morbidities which are thought to be mediated by a decrease of adipose tissue inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. We analyzed expression profiles in subcutaneous adipose tissue from 22 obese women before and 3 months after surgery using the RNA-seq technology. Of 15,972 detected genes, 1214 were differentially expressed after surgery. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, we identified 26 modules of coexpressed genes. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue, including a general signature of innate immune cells, an adaptive immune response elicited by T lymphocytes, a neutrophil-mediated inflammatory signature and an interferon-signaling pathway, respectively. After surgery, a few crucial molecules involved in chemotaxis and activation of immune cells were disconnected from their respective networks. These molecules may represent therapeutic targets against adipose inflammation. mRNA sequencing of subcutaneous adipose tissue (SAT) samples from 22 obese women before and 3 months after bariatric surgery
Project description:The main objective of this project is to compare the miRNA expression profile of paired visceral adipose tissue and skeletal muscle from obese patients undergoing bariatric surgery. More than 300 miRNAs were identified by Next Generation Sequencing technique in both the visceral adipose tissue and the skeletal muscle of six obese women undergoing bariatric surgery.
Project description:Genome-wide expression profiles in peripheral monocytes (PM) from 19 obese women before and 3 months after bariatric surgery using the RNA-seq technology. This dataset is linked to the dataset GSE65540 providing expression profiles in subcutaneous adipose tissue (SAT) in the same population. Due to exclusion of some individuals for technical reasons, the overlap between the 2 datasets is of 18 women.
Project description:Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is through the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant. Cecal contents were isolated from either obese controls that received sham surgery or formerly obese mice following bariatric surgery-induced weight loss and transferred by FMT to lean recipients. Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric-surgery treated mice. Microbes can impact tumor burden through microbially derived metabolites produced or modified by gut microbiota including branched chain amino acids (BCAA). Circulating BCAA correlated significantly with NK T cell content in the tumor microenvironment in both donor mice after bariatric surgery and in FMT recipients of donor cecal content after bariatric surgery compared to obese sham controls. Findings implicate a role of microbially-derived BCAA in activating anti-tumor immunity that is dependent upon bariatric surgery. Importantly, when stool from a patient who exhibited 25% weight loss post-bariatric surgery was transplanted into recipient mice and compared to the patient’s pre-bariatric surgery stool transplant. Patient samples post bariatric surgery significantly reduced tumor burden by 2.4-fold and immunotherapy effectiveness was doubled. Taken together, findings suggest that reinvigorating anti-tumor immunity may be dependent upon microbially derived metabolites such as BCAA.
Project description:Low-grade chronic inflammation plays an important role in the development of obesity and obesity-associated disorders such as insulin resistance, type 2 diabetes, the metabolic syndrome and atherosclerosis. One possible link between obesity and inflammation is the enhanced activation of circulating monocytes making them more prone to infiltration into the adipose and vascular tissues of obese persons. Furthermore, weight loss after bariatric surgery is associated with less inflammation. Transcriptome analysis of circulating monocytes from control and obese patients before and after bariatric surgery will potentially provide insights into the pathophysiology of obesity and associated disorders and supply biomarkers for diagnostic purpose. The cohort comprised 6 lean age-matched controls (BMI: 20.3±0.5 kg/m2, mean±SEM) and 18 obese individuals without clinical symptoms of cardiovascular disease (BMI: 45.1±1.4 kg/m2, P<0.001 compared with lean controls). These 18 morbidly obese subjects were referred to our hospital for bariatric surgery. Before they were included, individuals were evaluated by an endocrinologist, an abdominal surgeon, a psychologist and a dietician. Only after multidisciplinary deliberation, the selected patients received a laparoscopic Roux-en-Y gastric bypass. CD14+ monocytes were collected before and three months after bariatric surgery (BMI: 37.5±1.3 kg/m2, P<0.001 compared with before weight loss), total RNA was extracted and subjected to genome-wide expression analysis. Samples consisted of CD14+ monocytes from 6 lean controls and 18 morbidly obese patients before and three months after bariatric surgery. The 6 lean controls were also used to make 6 control pools.
Project description:In order to identify mechanisms underlying the long-term beneficial effect of bariatric surgery on abdominal subcutaneous WAT, we performed gene microarray analyses on adipose tissue from a cohort of obese women. Adipose tissue biopsies were obtained before RYGB, and then 2 and 5 years thereafter. To evaluate the long-term effect of Roux-en-Y gastric bypass (RYGB) surgery on WAT, we also compared the WAT gene expression at 5 years postsurgery with that of age-matched nonoperated women.
Project description:The molecular background of mitochondrial dysfunction in adipose tissue of morbidly obese individuals and bariatric surgery-induced changes in adipose mitochondrial function remain incompletely understood. To evaluate the mechanisms behind the surgery-induced changes and differences between morbidly obese subjects and nonobese controls, we performed a LC-MS/MS proteomics analysis of abdominal subcutaneous (SAT) and visceral adipose tissue samples (VAT) collected from the bariatric surgery, SAT samples collected 6 months after surgery, and control SAT and VAT samples collected from baseline.
Project description:This experiment was designed to study if there are differences in gene expression in the adipose tissue of women affected by polycystic ovary syndrome (PCOS) compared to non-hyperandrogenic women. PCOS is the most common endocrinopathy in women of reproductive age, and is characterized by hyperandrogenism and chronic anovulation. This disease is frequently associated with obesity, insulin resistance, and defects in insulin secretion, predisposing these women to type 2 diabetes, atherosclerosis, and cardiovascular disease. We have applied high-density oligonucleotide arrays to omental adipose tissue samples obtained from eight morbidly obese PCOS patients and seven morbidly obese non-PCOS women at the time of bariatric surgery. Keywords: Disease state analysis
Project description:Patients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese subjects undergoing bariatric surgery and then used for the mRNA expression analyses. mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500. This dataset is part of the TransQST collection.
Project description:Transcriptional profiling of subcutaneous adipose tissue before and after 2 years of bariatric surgery. This type of surgery produce a masive weight loss in morbidly obese subjects, and improve the comorbidities associated to obesity. Goal was to determine the effects of bariatric surgery on the gene expression of subcutaneous adipose tissue.